J. Am. Chem. SOC.1982, 104, 7059-7065 the bath was removed and stirring was continued for 20 min. Solvent was removed, and the product was purified by chromatography on silica gel (1 :9 ether-pentane) to give, after recrystallization from ether-pentane, 0.212 g (83%) of 1-phenylethyl 2-nitrophenyl sulfide: mp 90.5-91.5 OC; ‘H N M R 6 1.70 (d, J = 7 Hz, 3 H), 4.47 (q, J = 7 Hz, 1 H), 7.1-7.4 (m.8 H), 7.98 (d, J = 8 Hz, 1 H). Anal. Calcd for CI4H,,NO2S: C, 64.84; H, 5.05. Found: C, 64.81; H, 5.00. The sulfide prepared above (67 mg, 0.259 mmol) in 15 mL of CH2Cl2 was cooled to 0 OC, and 52 mg (0.258 mmol) of m-chloroperbenzoic acid was added. After 10 min, the reaction mixture was filtered through Celite, and solvent was removed from the filtrate. Crystallization from CH,C12-pentane gave 54.7 mg (77%) of 45 as yellow needles: mp 98-99 OC; ’H N M R (CDCI,, major diastereomer, 3:l ratio) 6 1.36 (d, J = 7 Hz, 3 H), 4.28 (q, J = 7 Hz, 3 H), 7.3-7.6 (m,5 H), 7.67 (t m, J = 8 Hz, 1 H), 7.93 (t m, J = 8 Hz, 1 H), 8.24 (d m,J = 8 Hz, 1 H), 8.27 (d m, J = 8 Hz, 1 H). The elimination rate was measured in CDCI, solution (0.2 M) containing 0.4 M Et2NH at 38 OC in the N M R probe, k = (1.39 f 0.09) x 10-5 s-1. 1-Pbenyletbyl 2,4-dinitropbenyl sulfoxide (46) was prepared by a procedure similar to one above. Sulfide: mp 109-1 10 O C ; IR 1590, 1535, 1518, 1355, 1340, 1055, 740, 705 cm-’; ‘H N M R 6 1.68 (d, J = 7 Hz, 3 H), 4.60 (q, J = 7 Hz, 1 H), 7.2-7.6 (m.6 H), 8.13 (dd, J = 9, 2 Hz, 1 H), 8.80 (d, J = 2 Hz, 1 H); MS 304.051 1 (M+), calcd for C14H12N204S,304.0523. Sulfoxide (46): lH N M R (CDCI,, partial) 6 4.25-4.3 (br q, J = 6 Hz), 8.65 (d, J = 8 Hz), 8.96 (s). Decomposed in CDCl, to styrene at 38 OC, k = 1.34 X lo4 s-l. Acknowledgment. W e thank t h e National Science Foundation a n d t h e Wisconsin Alumni Research Foundation for support of this work. Registry No. l a , 83333-70-4; l b , 68099-13-8; IC, 60174-90-5; 2a, 83333-71-5; 2b, 68099-15-0; 2c, 15619-32-6; 4, 68099-18-3; 5a, 1748864-1; Sb, 68099-38-7; 6, 31952-17-7; 7, 32363-86-3; 8, 68099-17-2; 9, 68099-19-4; (E)-10, 68099-20-7; (E)-11 (isomer l ) , 83333-72-6; E-11 (isomer 2), 83334-14-9; (E)-12, 83333-73-7; (2)-12, 83334-1 1-6; (E)-13,
7059
83333-74-8; (E)-14, 83333-75-9; (E)-15, 83333-76-0; (E)-16, 8333377-1; (E)-17, 83333-78-2; 18, 83333-79-3; (E)-19, 5284-13-9; (E)-20, 83333-80-6; (E)-21, 83333-81-7; 22a, 68099-24-1; 22b, 68099-25-2; 2212, 83333-82-8; 23a, 15619-34-8; 24, 83333-83-9; 25, 21473-05-2; 26, 57293-43-3; (E)-27,68099-28-5; (2)-27, 83334-03-6; (E,E)-28,6809929-6; (E,Z)-28, 68099-40-1; (E)-29, 77605-16-4; (Z)-29, 77605-17-5; (E)-30, 83333-84-0; (Z)-30, 83334-04-7; (E)-31, 55 177-38-3; (Z,E)-32, 83333-85-1; (E,E)-32, 83334-12-7; (Z,Z)-32, 83334-13-8; (E,E)-33, 83333-86-2; (Z,E)-33, 83334-05-8; (Z,E)-34, 83333-87-3; 35, 8333388-4; (E)-36, 83333-89-5; (2)-36, 83334-06-9; (E)-37, 83333-90-8; (2)-37, 83334-07-0; (E)-38, 83333-91-9; 40 (isomer l), 83333-92-0; 40 (isomer 2), 83333-93-1; 42a, 83333-94-2; 42b, 83333-95-3; 43a, 8333396-4; 43b, 83333-97-5; 44, 83333-98-6; 45, 83333-99-7; 46, 83334-00-3; PhLi, 591-51-5; 4-methyl-2-nitrobenzeneselenenylchloride, 68099-14-9; 4-methyl-2-nitrophenylselenocyanate,65275-29-8; 4-methyl-2-nitrophenyl methyl selenide, 83334-01-4; 2-iodotoluene, 61 5-37-2; 2-cyclohexenone, 930-68-7; prenyl phenyl selenide, 69690-81-9; 1-bromo-3phenylpropane, 637-59-2; butyl phenyl selenide, 28622-6 1-9; 2-phenylpropionaldehyde, 93-53-8; propenyl bromide, 590- 14-7; 1-decyne, 76493-2; crotonaldehyde, 4170-30-3; 2-phenyl-3-penten-2-01, 4743-67-3; 4-bromo-3-phenyl-2-pentanone,83334-02-5; allyl phenyl selenide, 14370-82-2; acetophenone, 98-86-2; phenyl (4-phenyl- 1-penten-4-ol-3-yl) selenide, 83334-08- 1 ; phenyl (4-phenyl-2-penten-4-01-1-yl) selenide, 83334-09-2; 4-phenyl-2-pentene-l,4-diol,83334-10-5; 2,4-dinitrobenzenesulfenyl chloride, 528-76-7; l-phenyl-4-frans-methylcyclohexanol, 30689-84-0; l-phenyl-4-cis-methyIcyclohexanol, 30689-83-9; 4-methylcyclohexenone, 55 15-76-4; 2,5-dichloroiodobenzene,29682-41-5; 4methyl-2-cyclohexenone, 55 15-76-4; 2-nitrophenylthiocyanate,2769-30-4; 1-phenylethanol, 98-85-1; I-phenylethyl 2-nitrophenyl sulfide, 1975858-8. Supplementary Material Available: Spectroscopic d a t a a n d / o r experimental details for t h e preparation of t h e following compounds: 2,4-dinitrobenzeneselenocyanate,2,4-dinitrobenzeneselenenyl bromide, I C , 4, 6, 8, 9, 14, 18, 19, 20, 21, 40, a n d 41 ( 5 pages). Ordering information is given on any current masthead page.
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Induced Circular Dichroism of P-Cyclodextrin Complexes with Azanaphthalenes-Polarization Directions of the T* 7r Transitions in Azanaphthalenes Hiroshi Shimizu,? Akira Kaito,? and Masahiro Hatano* Contribution from the Chemical Research Institute of Non-aqueous Solutions, Tohoku University, Sendai 980, Japan. Received August 17, 1981
Abstract: The induced circular dichroism (ICD) spectra of the @-cyclodextrin (0-CD,) complexes with mono-, di-, and triazanaphthalenes were measured in the wavelength region 200-400 nm. The polarization analysis and spectral assignments of these azanaphthalenes were made from the comparison of the theoretical results calculated by using the C N D O / S - C I approximation with the observed I C D spectra. The polarization directions of the first a* a transitions in azanaphthalenes a r e closely related to the position of aza nitrogen atoms and can be determined by the coefficients of the configurations in the corresponding lowest a* a states. From the observation of the ICD band with mixed signs, the presence of the “forbidden” character is strongly suggested in the second absorption bands of isoquinoline, phthalazine, cinnoline, and quinazoline. In each case of azanaphthalenes, the observation of positive I C D bands in the third absorption band indicated the predominance of the long-axis-polarized electronic transitions.
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Polarization analysis is one of t h e most useful techniques for spectral assignments of a r o m a t i c compounds, since it offers information on t h e transition-moment directions a n d vibronic structure. T h e measurements of polarized o r linear dichroism’ spectra require a partially oriented assembly of molecules achieved by t h e preparation of single a n d mixed crystal^,^^' t h e dispersion ‘Present address: Research Institute for Polymers and Textiles, 1-1-4, Yatabe-Higashi, Tsukuba, Ibaraki 305, Japan.
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of solute molecules in nematic liquid crystal4 and stretched polymer t h e application of electric o r magnetic fieldsss9 a n d hy(1) Linear dichroism is defined as the difference in absorbance found when linearly polarized light with the electric vectors in two directions, perpendicular to each other, is used. (a) B. Norden, Appl. Spectrosc. Reu., 14, 157 (1978); (b) E. W. Thulstrup, “Aspects of the Linear and Magnetic Circular Dichroism of Planar Organic Molecules”, Springer-Verlag, Berlin, 1980. (2) D. S. McClure, J . Chem. Phys., 22, 1668 (1954); 24 1 (1956); 25,481 (1956); J. W. Sidmann and D. S.McClure, ibid., 24, 757 (1956).
0002-7863/82/1504-7059$01.25/0 0 1982 American Chemical Society
Shimizu, Kaito, and Hatano
1060 J . Am. Chem. SOC.,Vol. 104, No. 25, 1982 drodynamic shear,1° and the principle of photoselection." Thulstrup et al. have analzyed the linear dichroism spectra in the stretched polymer sheet by the introduction of the observable orientation parameters and applied their method to a variety of organic aromatic molecules.6Jz The direction of the electronic transition moments of organic aromatic compounds have been also studied on the basis of the signs of the extrinsic circular dichroism spectra measured in the cholesteric liquid crystal solution^.'^ On the other hand, the induced circular dichroism (ICD) of /3-cyclodextrin (p-CD,) complexes with organic aromatic compounds has been shown to be useful for the determination of the relative direction of electronic transition dipole moment of the organic aromatic compound^.'^-'^ ICD is the phenomenon in which the circular dichroism (CD) can be induced at the absorption frequency of the achiral molecule by the dissymmetric perturbation of the chiral species. In the case of the p-CD, inclusion complex, CD is expected to be induced at the absorption bands of the achiral guest molecules that are included in the cavity of the P-CD, host molecule, since 6-CD, is composed of chiral glucose units. The ICD method using inclusion phenomena of p-CD, has some limitations; this method cannot be applied to the quantitative determination of the polarization angles in molecules of low symmetry and to separation of strongly overlapping transitions of opposite polarization. The ICD method is, however, said to be a new and simple technique for the study of the polarization direction of the electronic transition, which does not require any elaborate instrumentation. Harata and Uedaira14 have recently measured the ICD spectra of P-CD, complexes with naphthalene derivatives and determined the structure of the p-CD, complexes on the basis of the calculation of the rotational strengths by the Kirkwood-Tinoco e q ~ a t i 0 n . l ~ Yamaguchi et al. have studied the ICD spectra of p-CD, complexes with 2-hydro~ytropone'~ and azulene16 and have discussed the direction of the electronic transition moment of the guest molecules. In our previous papers,I7J8we have studied the ICD spectra of p-CD, inclusion complexes with a series of substituted benzenes in aqueous solution and have shown that the sign and intensity of ICD spectra depend on the transition-moment directions of substituted benzenes that are included in the cavity of @-CD,. On the other hand, the electronic structure of azanaphthalenes has received much Theoretical investigations have
(3) F. Dorr and M. Held, Angew. Chem., 72,287 (1960);F. Dorr, ibid., 78, 457 (1966). (4) (a) E. Sackmann, J . Am. Chem. SOC.,90, 3569 (1968); (b) G. P. Ceasar and H. B. Gray, ibid., 91, 191 (1969). (S) Y. Tanizaki, Bull. Chem. Soc. Jpn., 38, 1798 (1965);T. Hoshi and Y. Tanizaki, Z.Phys. Chem., Wiesbaden, 71,230 (1970);T. Hoshi, H. Inoue, J. Shiraishi, and Y. Tanizaki, Bull. Chem. SOC.Jpn., 44, 1743 (1971). (6) E. W. Thulstrup and J. H. Eggers, Chem. Phys. Left.,1,690 (1968); E. W. Thulstrup, J. Michl, and J. H. Eggers, J . Phys. Chem., 74,3868 (1970); J. Michl, E. W. Thulstrup, and J. H. Eggers, ibid., 74,3878 (1970). (7) Y. Matsuoka and K. Yamaoka, Bull. Chem. Soc. Jpn., 52,2244,3163 (1979). (8) (a) W. Kuhn, H. Diihrkopp, and H. Martin, Z . Phys. Chem., A b f . B, 845, 121 (1940); (b) H. Labhart, Helu. Chim. Acfa, 44,447,457(1961). (9)J. Breton and G. Paillotin, Biochim. Biophys. Acta, 459, 58 (1977). (10) A. Wada, Appl. Specfrosc. Reu., 6,1 (1972). (1 1) A. C.Albrecht, J . Mol. Specfrosc.,6,84 (1961);A. C. Albrecht and W. T. Simpson, J . Am. Chem. Soc., 77,4454(1955);A. H. Kalantar and A. C. Albrecht, Ber. Bunsenges. Phys. Chem., 68, 361 (1964). (12) E. W. Thulstrup and J. Michl, J . Phys. Chem., 84, 82 (1980). (13) (a) E.Sackmann and J. Voss, Chem. Phys. Left., 14,528 (1972); (b) W. G. Hill, S.F. Mason, and R. D. Peacock, J . Chem. SOC.,Perkin Trans. 2, 1262,(1977). (14) K. Harata and H. Uedaira, Bull. Chem. SOC.Jpn., 48,375 (1975). (15) H. Yamaguchi, N.Ikeda, F. Hirayama, and K. Uekama, Chem. Phys. Left.,55,75 (1978). (16) N. Ikeda and H. Yamaguchi, Chem. Phys. Lett., 56, 167 (1978). (17) H. Shimizu, A. Kaito, and M. Hatano, Bull. Chem. Soc. Jpn., 52, 2678 (1979). (18) H. Shimizu, A. Kaito, and M. Hatano, Bull. Chem. Soc. Jpn., 54,513 (1981). (19) I. Tinoco, Jr., Adu. Chem. Phys., 4, 113 (1962). (20)G. Favini, I. Vandoni, and M. Simonetta, Theor. Chim.Acta, 3,45 (1965).
Tabte 1. Averaged Wavenumber of the Electronic Transitions ( ~ j and ) Polarizability (a)of the Bonds in a Glucose Residue (@~~-@II)X
bonds
l o z 4 ,cm3
c-c c-oc
O.7lb 0.43c 0.45d
0-H
v b j x i0-3,a
cm-' 70.85e'f 67.539~~ 80.7 8g-
q,' is approximated by a wavenumber midway between the first a6sorption band and its ionization potential. C. G. LeFevre R. J. W. and J. W. LeFevre, J. Chem. Soc., 3549, (1956). LeFevre et al., ibid., 479, (1963). C. G . LeFevre et al., ibid., 123, (1960). e L. W. Pickett et al.,J. A m . Chem. Soc., 7 3 , 4 8 6 2 (1951). R. F. Pottie et al., ibid., 8 3 , 3204 (1961). A . J. Harrison e t al., J. Chem. Phys., 3 0 , 3 5 5 (1959). K. Watanabe, ibid., 26, 542 (1957). a
Figure 1. Coordinates of ei.
been performed to interpret the electronic spectra of azanaphthalenes within the semiempirical SCF-MO framework.2w24 Furthermore, the photoelectron spectra of azanaphthalenes were measured, and the ordering of the a orbitals and the nitrogen "lone-pair" orbitals was d i s ~ u s s e d .Similarly, ~ ~ ~ ~ ~ from the viewpoint of the location and ordering of the a* n and low-lying a* a electronic transitions, the electronic spectra of azanaphthalenes have been observed in vapor phasez7 or in mixed crystals.28 Despite these theoretical and experimental investigations, there are some unsettled problems with respect to the electronic-band assignments of azanaphthalenes. Recently, the magnetic circular dichroism (MCD) spectra of azanaphthalenes were reported and the spectral assignments of these molecules were examined on the basis of the Faraday B term~.~~J~ In this paper, we measured the ICD spectra of P-CD, complexes with mono-, di-, and triazanaphthalenes in aqueous solution and discussed the polarization directions of these azanaphthalenes by the comparison with the results calculated by using CNDO/S-CI appro~imation.~ We ~ also attempt to derive the dependence of the ICD spectra on the polarization directions of the guest molecule from the theoretical model developed by Kirkwood-Tinoco.19
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Experimental Section 6-CD, and azanaphthalenes were commercially available. p-CD, was purified by recrystallization from aqueous solution. Phthalazine, quinazoline, and pyrido[2,3-b]pyrazine were recrystallized from ether, petroleum ether, and petroleum ether-ethanol (9:l v/v), respectively. Quinoline, isoquinoline, and quinoxaline were distilled under reduced
(21)J. Koutecky, J . Chem. Phys., 47, 1501 (1967). (22) H. Baba and I . Yamazaki, J . Mol. Spectrosc., 44, 118 (1972). (23)J. E. Ridley and M. C. Zerner, J . Mol. Spectrosc., 50, 457 (1974). (24) A. Kaito and M. Hatano, J . Am. Chem. SOC.,100, 4037 (1978). (25) D. M.W. van der Ham and D. van der Meer, Chem. Phys. Lelf., 12, 447 (1972). (26) F. Brogli, E. Heilbronner, and T. Kobayashi, Helu. Chim. Acta, 55, 274 (1972). (27) (a) R. W. Glasses, L. C. Robertson, and J. A. Merritt, J . Chem. Phys., 53, 3857 (1970); (b) S . C. Wait, Jr., and F. M. Grogan, J . Mol. Spectrosc., 24, 383 (1967); (c) G. Fischer, A. D. Jordan, and I. G. Ross, ibid., 40,397 (1971). (28) (a) A. D. Jordan, G. Fisher, K. Rokos, and I. G. Ross, J . Mol. Specfrosc., 45, 173 (1973); (b) G . Fisher, ibid., 49, 201 (1974); (c) A. D. Jordan, I. G. Ross, R. Hoffmann, J. R. Swenson, and R. Gleiter, Chem. Phys. Left., 10, 572 (1971). (29) M. Vasak, M. W. Whipple, and J. Michl, J . Am. Chem. SOC.,100, 6838 (1978). (30) J. Del Bene and H. H. Jaffe, J . Chem. Phys., 48, 1807 (1968). ~~
J. Am. Chem. Soc., Vol. 104, No. 25, 1982 7061
Circular Dichroism of P-Cyclodextrin Complexes pressure. Cinnoline was purified by vacuum sublimation before use. 1,5-Naphthyridinewas used without further purification (Tokyo Kasei Co., Ltd.). An inclusion complex was prepared by mixing p-CD, and the corresponding azanaphthalene in an aqueous solution or in aqueous KOH. The circular dichroism and absorption spectra were measured at room temperature on a JASCO 5-500 circular dichrograph with a J-DP 500 data processor and a Hitachi EPS-3T recording spectrophotometer,respectively. In this paper, molar ellipticity was normalized by the concentration of the guest molecule.
Vbj of the bonds in 6-CD,. Then, each of components of R,,, at a transition wavenumber vai is computed by the summation over all values ofj, with the values of (a33- a l l )and vbJ listed in Table I. In this calculation the contributions of the C-C, C-0, and O-H bonds in p-CD, are taken into account. The effect of all the C-H bonds is neglected, since these bonds may have isotropic polarizability. Among the evaluated components of Rib, the following relations have been found to be held, because the p-CD, has a 7-fold axis.
Theory Dependence of the Theoretical Rotational Strength on the Transition-Moment Directions of the Guest Molecule. The rotational strength is a fundamental quantity in circular dichroism. In the p-CD,-aromatic compound systems, the theoretical rotational strength (Rioa)of the transition from the ground state 0 to the excited state a in an aromatic compound is expressed as in eq 1, developed by Kirkwood and Tinoco: Here ej is the unit
(7)
R , = -Ryx R,, = -R zx R,, = -2R,,
Rxx = Ryy
Rzy
= -Ryr
By using these relations, we can obtain the final form of RIOa expressed as
R~~~ = -(3 1 COS^ 2
e - i ) ~ ,=, -21( 3
cos2 e - i)~c,,aZx R,,
(8)
In eq 8, the sign of RiOadepends only on the angle 0, since both R,, are positive values. Therefore, eq 8 suggests that the absolute direction of the transition dipole moment is determined by only the sign of observed ICD spectra, when the structure of inclusion complexes can be regarded as the axial inclusion in which the long axis of the guest molecule is parallel to the axis of the p-CD, cavity ( z axis). On the contrary, the relationship in eq 7, R,, = Ruy,implies that we can make no reference to the difference in the geometrical environment of the guest molecule with respect to the x and y axes. That is to say, in this theoretical model, the orientation of the guest molecule in the xz plane is equivalent to that in the yz plane. From the same reason, it is also suggested that the a* n (out of plane) transition may give rise to the negative ICD band as well as the short-axis-polarized a* a (in plane) transition when the guest molecule is included by the axial inclusion. pLioa2 and
vector in the direction of the symmetry axis of the bond in p-CD,; e, is the unit vector in the direction of the electric dipole moment (iiioa)of the transition from the ground state (0) to the excited state (a) in the guest molecule, and vai is its wavenumber; and a l l are bond polarizabilities at zero frequency parallel and perpendicular, respectively, to the symmetry axis of the bond in p-CD,; rij is the vector pointing from the center of the guest molecule to each bond in p-CD,; and vb, is the averaged wavenumber of the electronic transitions of the bond in p-CD,. In this paper, v b j is approximated by a wavenumber midway between the first absorption band in the bond of p-CD, and its ionization potential. The values of ( a j 3- a l l )and vbj for each bond are listed in Table I. In the first place, the origin of the coordinates was chosen in the center of a ring of 6-CD, that was assumed to have a 7-fold symmetry axis. Next, e,, which is put at the origin of the pCD,-fixed Cartesian coordinates, is expressed by the spherical polar coordinates (Figure 1 ) resulting in eq 3. Here tl is the
e, = (sin 0 cos $)i
+ (sin 0 sin $)j + (cos 6)k
(3)
inclination angle of e, with respect to the z axis (the symmetry axis of p-CD,), while $ is the angle in which the projection of ei into the xy plane inclines to the x axis. In eq 3, i, j, and k are the orthogonal unit vectors along the x, y , and z axes, respectively, of the Cartesian coordinates. After substitution of eq 3 into eq 1, eq 1 can be expressed in terms of the angles 0 and 4. Then, rotational strength (Rioa)is given by expression 4:
+
+
RiOa= (sin' O)[R,,(cos2 4) + Ryy(sin24) ( R , R,) X (cos $)(sin $)I + (sin B)(cos B)[(R,, + RZx)(cos$) (Ryz+ Rzy)(sin $)I + (cos2 (4)
+
w,,
where
Rzz = avaipioa2 E J
vbj2(a33
- a1l)j(GF)zz
vbt
-
(5)
Here R,, is the zz component of Rioaand contains the geometry factor (GFe),, defined by eq 6. Each of other eight components of Rioacan be expressed in a similar manner as above. All the components of RiOahave two quantities in common, the bond polarizability difference (a33- a11) and averaged wavenumber
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Results and Discussion ICD Spectra and Polarization Directions. Figures 2-9 show the CD (upper) and UV (lower) spectra of the p-CD, complexes with azanaphthalenes in aqueous solution. In each figure, ICD bands were observed at absorption frequencies of achiral azanaphthalenes. In these figures, the vertical lines indicate the theoretical spectra calculated by using the CNDO/S-CI method,24 with the lengths of the lines representing relative values of oscillator strengths. The open circle designates the a* n transition at the frequency calculated. Numbers (1, 2, 3, ...) designate in turn the first a* a,the second a* a,the third a* K transitions of azanaphthalenes, and so on, respectively. The broken lines in structural formulas indicate the calculated directions of the respective transition dipole moments. Figure 2 shows the CD and UV spectra of the p-CD, complex with quinoline, which contains a nitrogen atom a t the CL position. In this case, a positive ICD band with the vibrational structure observed in the lower wavenumber region was assigned to the first a* a transition, while a tranone negative CD band was induced by the second K * sition in the middle-wavenumber region. In the higher wavenumber region, a large positive ICD band originating from the third a* a transition was observed. As shown in this figure, the sign of the ICD bands are in agreement with the theoretical results in which the polarization directions of the first R* a, the second a* a, and the third a* a transitions of quinoline are nearly long, short, and long axes, respectively. As shown in Figure 3, the p-CD, complex with isoquinoline exhibited two negative ICD bands in the longer wavelength region, and these bands were attributed to the first and the second K * a transitions, which were both evaluated to be the roughly short-axis polarizations. One intensive positive CD band derived from the third and the fourth a* a transitions was observed in the shorter wavelength region and coincided with the calculated results in which both of the a* a transitions were approximately long-axis polarized. In the case of the P-CD,-quinoxaline system, a weak negative CD band was induced by the a* n transition at 370 nm (Figure 4). Although the second absorption band of quinoxaline was supposed to be composed of the first T* R ('Al
-
-
+ -
+-
- -
-
+-
-
+ -
-
-
-
-
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Shimizu, Kaito, and Hatano
1062 J. Am. Chem. Soc.. Vol. 104, No. 25, 1982
3 45
x 10-3
/
3
c m-1
35
40
30
50
45
40
x 10-3
/
cm-1
35
30
25
1.0 r
-g
r
1.0
9 E
E
P
p
"E
p
0.5
;
'FI
\
U
0.5
\
B
t
0
a
h
x
0
s2
0 left
sca Ie
scale
3
1
4 c
k 2
x
0
9,
\I
, ,
3
E
2 2 1
\ U
t
o -1
scale
-2
7 6
7
E
4E
5
i
4
9
E
3
2
0
1
scale
k
)
0 I
220
350
400
-
the positive CD band originated from the 'A, 'Al transition predominates the adjacent one derived from the IB2 IA, transition. A large positive ICD band observed at 230 nm was assigned to the third a* a (IA, 'Al) transition, Le., long-axis polarization. Figure 5 shows the CD and UV spectra of 1,Snaphthyridine with C2, symmetry. From lower to higher wavenumber region, the signs of ICD bands observed were positive, negative, and positive, respectively. These results were in accord with the theoretical directions of the transition dipole moments, and each of these a* a transitions was attributed to the 'B, lA, transition. As shown in Figure 6, the first K* a transition, which was 'A, transition of phthalazine, gave rise to assigned to the 'A, a positive ICD band. While the observation of two a* n transitions of phthalazine was r e p ~ r t e d *in ~ .the ~ ~ lower wavenumber region, the CD band originating from the a* n transition was hidden by the first a* K transition. On the contrary, the ICD band with two different signs was observed in the middle-wavenumber region (35 000-42 000 cm-') corresponding to the second absorption band of phthalazine. From the results calculated by using the CNDO/S-CI method, it is considered that there exists only an origin of the electronic transition, Le., the second a* a ('B2 'Al) transition in this region. This result indicates the presence of "forbidden" character in the second absorption band, since the mixed polarization was observed in a single allowed electronic t r a n ~ i t i o n . ~ ~In other words, the "borrowed" long-axis-polarized moment was considered to be induced by the vibronic coupling with the adjacent intensive absorption band attributed to the third a* a ('A, 'Al) transition. In this case, the nontotally symmetric vibration mode, b2,
- -
-
-
-
+
-
u v
+
- -
2
A
/ n m
Figure 3. CD (upper) and UV (lower) spectra of the @-CD,complex with isoquinoline in 1.0 X IO4 M aqueous KOH (pH 9.06): @-CD, (1.589 X lo-* M) + isoquinoline (3.390 X lo4 M).
-
300
X / nm Figure 4. CD (upper) and UV (lower) spectra of the @-CD,complex with quinoxaline in aqueous solution: (broken line) in the absence of @-CD,,(solid line) @-CD,(1.465 X M) quinoxaline (1.990 X lo4 MI.
-
ight
left
250
+
4
E p
200
30
I
1
0
+
/ cm-1 35
40
45
50
X
w
w
h / nm Figure 2. CD (upper) and UV (lower) spectra of the @-CD, complex with quinoline in 1.0 X M aqueous KOH (pH 7.45): (broken line) in the absence of @-CD,,(solid line) b-CD, (1.438 X lO-* M) + quinoline (3.226 X M). x 10-3
5!
x
9 1
3
m I
70 1
l
0
f
E \
E
w
P
0
1-
\
8
'
2
1-
P
x
E
0
a
B
m ;
4E
-
C'
P
-
E
% 3 2
-
- -
'Al) and the second K * K (IB2 'Al) transitions, only a positive ICD band was observed at 320 nm. This suggests that
- -
(31) R. M. Hochstrasser and D. A. Wiersma, J . Chem. Phys., 56, 528 ( 1972). (32) A. C. Albrecht, J . Chem. Phys., 33, 156 (1960).
Circular Dichroism of p- Cyclodextrin Complexes
3 50
45
/
x 10-3
40
J. Am. Chem. Soc., Vol. 104,No. 25, I982 7063
-
cm-3
1 0 - ~ / cm-1 30
-J x
35
50
30
e
?-
45
40
35
25
,
1.0
9
N
0.5
4
\ P
O
z X -0.5
left sca Ie
32
v
c D -4 8
left scale
7
IE
7
0
0
E 9 r 1-
\
E
w
4
\
0
220
260
240
$ 50
280
300
?
c 1-
6 4
4
2
:
\ 0
45
10-3
40
/
I
2 1
,-I
35
x
w
1
0
n m
0 200
250
ol
\
o
300
h
350
400
/nm
Figure 7. CD (upper) and UV (lower) spectra of the p-CD, complex with cinnoline in aqueous solution: (broken line) in the absnece of p-CD,, (solid line) &CD, (1.270 X lo-* M) + cinnoline (3.750 X M).
-
30
r
P N E 0
2
3
340-
320
a $
z
z X
Figure 5. CD (upper) and UV (lower) spectra of the p-CD, complex with 1,5-naphthyridinein aqueous solution: (broken line) in the absence of 8-CD,, (solid line) P-CD, (1.434 X M) + 1,Snaphthyridine (2.035 X lo4 M).
-
in Figure 7, exhibited a weak negative CD band that was derived from the a* n transition at 380 nm. The first a* a transition resulted in a negative CD band at 320 nm, and this is assigned to the short-axis-polarized a* a (lA' ]A') transition. Although the second a* a transition of cinnoline was evaluated to the nearly short-axis polarization, the ICD band with mixed signs was observed in the region corresponding to the second absorption band, similar to the case of phthalazine. It was supposed that the component of the long-axis-polarized moment in the second absorption band was caused by intensity borrowing through the vibronic interaction with the adjacent third a* a transition, which is approximated long-axis polarized. For the polarization directions of the first a* ir and the second a* a transitions of cinnoline, Ridley and Z e r r ~ e using r ~ ~ the INDO technique have reported results different from our calculation^.^^ They evaluated the polarizations of both a* a transitions to the intermediate directions between long and short axes, whereas our calculation predicted short-axis polarization for these electronic transitions. Two negative ICD bands observed in this spectral region were in reasonable accord with our calculation. Figures 8 and 9 depict the spectra of quinazoline and pyrido[2,3-b]pyrazine, respectively. The first a* a transition of quinazoline was assigned to the short-axis polarized 'A' 'A' transition, while the sign of the CD band that was induced by the first a* a transition of pyrido[2,3-b]pyrazine was negative. In analogy with the case of phthalazine and cinnoline, the feature of the mixed polarization was observed in the second absorption band of quinazoline. This result also suggests the presence of the vibronic coupling in the second band. The totally symmetric vibration a' for the molecule with C, symmetry such as cinnoline and quinazoline seems to play an important role in the intensity borrowing by the vibronic interaction. The ICD band of pyrido[2,3-b]pyrazine in the shorter wavelength region could not be practically measured because of the poor signal to noise ratio. Origin of the Polarization Directions of the Lowest ?r* a States. It should be noted that the polarization directions of the
- - -
-
-2
E
4
P
2
h /
s
'E L! E
3
n
$ 1-
"200
T
c
5
E
r
n
E
I
'
mu
6
P
ex
right
-
--2
x 10
-4
-
+
+
r
IE m0
-
E
P
L
- -
o E 4
\ P
zx
2
0
n -
200
4 220
240
260
280
h /
300
320
0 340
nm
Figure 6. CD (upper) and UV (lower) spectra of the 0-CD, complex with phthalazine in aqueous solution: (broken line) in the absence of 8-CD,, (solid line) 0-CD, (1.428 X lo-* M) + phthalazine (3.240 X lod M).
is considered to contribute the vibronic coupling. The p-CD, complex with cinnoline (cu,@-diazanaphthalene),as demonstrated
-
+-
7064 J. A m . Chem. SOC.,Vol. 104, No. 25, 1982
7 50
45
/
x 10-3
40
Table 11. State Functions of the First rr*
m-1
35
30
,,
I
.
c
S h i m i z u , Kaito. and Hatano
compound
hydrocarbons and given the important rules,21two of which are summarized as follows. Rule 1: When one of the LCAO-MO coefficients of the atomic orbitals on the heteroatom in the two highest occupied molecular orbitals, 44 and 45, is small, the electronic configuration la) = ( q 4 - 6 - \k5,7)/2112 does not mix with ( p ) = q5-6 so much and the transition moments of the first two transitions are approximately orthogonal. (q+,stands for the one-electron-excitation configuration from the molecular orbital (MO) dito the MO q,.) Rule 2: On the contrary, when both of these LCAO-MO coefficients are large, a considerable mixing between ( a )and Ip) takes place and the first two transitions have parallel transition moments. The experimental and calculated results in the present work coincide with these theoretical considerations.21 As shown in Table 11, the lowest a* a state of azanaphthalenes is approximately expressed as a linear combination of the configurations $4-6, $5-.7, and $5-6, namely,
I
n
4 r
IE
$0
c 1-
E"
\
-
P
b w
$1
X
/ n m
Figure 8. C D (upper) and UV (lower) spectra of the 0-CD, complex with quinazoline in aqueous solution: (broken line) in the absence of 0-CD,, (solid line) 0-CD, (1.406 X M) quinazoline (5.035 X lo4 MI.
+
3 50
45
/
x 10-3
40
=
cl$4-6
-
c2$5-7
(9)
proper tie^:^^
cm-1
30
35
(441my146)
=
(451mY147) = my E
(10) (1 1)
mz
where my and m, are they and z components of the one-electron operator of the electric moments.34 From eq 9 to 11, the electric transition moment between ground state ($o) and excited state (q)is expressed as
P
\
NI
s! x
.s - 4 h
($olMI$l) = 2lI2(C1 - CZ)myj+ 2'i2C3m,k
t
x 3
right
(12)
where j and k are the unit vectors along the y and z axes, respectively. Then, the polarization direction of the lowest a* a transition is determined by the relative magnitude of the coefficients Cl-C3. Quinoline, quinoxaline, 1,5-naphthyridine, and pyrido[ 2 , 3 4 1 pyrazine, which are aza substituted at the a position, correspond to the case of rule 1. In this case, the lowest a* a state is mainly constituted of the configurations +4d and and contamination of $5-6 to the lowest a* a state is very small. As C3is very a small, the electric transition moment of the lowest a* transition of a-azanaphthalenes dominantly arises from the difference between C, and C, (see eq 12) and is nearly parallel to the y axis (long axis). On the other hand, in the case of P-azanaphthalene (isoquinoline) and a,@-diazanaphthalene (cinnoline, quinazoline), the electronic configurations $4+ and +5-7 strongly mix with q5+, according to rule 2. As C, has a large value, the polarization direction of the lowest T * a transition is approximately parallel to the z axis (short axis), similar to the second a* a transition. Although phthalazine contains aza nitrogen atoms at the @ position, the polarization direction of the lowest a* a transition
+
3
e
+ c3$5-6
where the coefficients C1, C,, and C3are taken to be positive. For quinoxaline and phthalazine, which belong to the C, point group, C3 is zero. Between molecular integrals of the electric moment operator, the following relations are obtained by using alternant pairing
(4'51m2146)
r
rr States
quinoline isoquinoline quinoxaline 1,j-naphthyridine ph thalazine cinnoline quinazoline pyrido [ 2,3-b ] pyrazine
sca Ie
scale
+-
-
2
\
-
+
n
-
200
220
240
260
h
280
300
320
340-
/ n m
Figure 9. C D (upper) and UV (lower) spectra of the @-CD, complex with pyrido[2,3-b]pyrazine in aqueous solution: (broken line) in the M) + pyrido[2,3absence of 8-CD,, (solid line) 8-CD, (1.433 X blpyrazine (3.894 X lo4 M).
-
+
+-
first a* a transitions in azanaphthalenes are very sensitive to the position and number of aza nitrogen atoms. Koutecky has reported the theoretical analysis on the transition moments of the lowest two a* a transitions of heteroanalogues of alternant +
-
(33) J. Michl, J . Chem. Phys., 61, 4270 (1974). (34) They and I axes are chosen as the long and short axes, respectively, of naphthalene, and the x axis is set perpendicular to the molecular plane.
J . A m . Chem. Soc. 1982, 104, 7065-7068
is parallel to the long axis. This is because $s-.6 and (C1$4-.6C,+,,,) belong to the different irreducible representations of the symmetry group C, and do not mix with each other. As a result, aza substitution at the @ position is considered to cause the short-axis polarization, except for phthalazine, for which the polarization direction is determined by symmetry rule. On the other hand, a-azanaphthalene holds to the same polarization direction as that of naphthalene, which is long-axis polarized.
Conclusion The ICD spectra of the @-CD, complexes with some azanaphthalenes were measured in the wavelength region 200-400 nm. For quinoxaline and cinnoline, weak negative CD bands were induced by the lowest allowed a* n transition. The polarizaion directions of the first a* a transitions in azanaphthalenes are closely associated with the location of aza nitrogen atoms and can be evaluated by the coefficents of the
-
+-
7065
configurations in the corresponding lowest R* P states. From the observation of the ICD band with mixed signs, the presence of the forbidden character is strongly suggested in the second absorption bands of isoquinoline, phthalazine, cinnoline, and quinazoline. Though the third absorption band in each case of azanaphthalenes was regarded as the mixture of a* a states composed of many configurations, the observation of positive ICD bands in this region indicated the predominance of the longaxis-polarized electronic transitions. Finally, it can be mentioned that the ICD method using the inclusion phenomena of @-CD, is a useful tool for the analysis of the polarization in the aromatic molecules. +-
+-
Registry No. 8-Cyclodextrin.quinoline,83528-62-5;0-cyclodextrin. isoquinoline, 83528-63-6;@-cyclodextrin-quinoxaline,83528-64-7;@cy-
clodextrin.1,5-naphthyridine, 83542-59-0;@-cyclodextrin.phthalazine, 83528-65-8;fl-cyclodextrin.cinnoline,83528-66-9;0-cyclodextrin.quin83528-67-0. azoline, 83542-53-4;@-cyclodextrin~pyrido[2,3-b]pyrazine,
A New Total Synthesis of the Fungal Toxin Slaframine Richard A. Gobao, Martin L. Bremmer, and Steven M. Weinreb* Contribution f r o m the Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802. Received April 21 1982
Abstract: Slaframine (1) has been synthesized from diene aldehyde 2. An intramolecular imino Diels-Alder reaction has been used to produce the indolizidine skeleton and to establish the requisite stereochemistry of this fungal metabolite.
Slaframine (l), a neutrotoxic metabolite of Rhizoctonia le-
Scheme I OSit-BuMe,
0
II
"''C0,Me
""'C0,Me
1 -
guminicola, is responsible for a disease characterized by excessive salivation in ruminants foraging on fungus-infected red clover hay.' The structure and absolute stereochemistry of this alkaloid were established by Rinehart et aL2 in 1968. Aust has found that slaframine itself is not bioactive, but is oxidatively transformed in vivo to a compound that can then interact with muscarinic acetylcholine receptors, producing the observed symptom^.^ Work has also appeared recently on the biosynthesis of l.4 To date, two total syntheses of slaframine have been reported.s Both relied heavily on classical Dieckmann chemistry to generate the indolizidine skeleton and upon catalytic hydrogenation to establish the three chiral centers of 1. The first slaframine synthesissa was nonstereoselective, but aided in confirmation of the proposed structure assignment. The second incorporated better stereo(1) Rainey, D. P.; Smalley, E. B.; Crump, M. H.; Strong, F. M. Nature (London) 1965, 205, 203. Aust, S. D.; Broquist, H. P. Ibid. 1965, 205, 204. (2) Gardiner, R.A,; Rinehart, K. L.; Snyder, J. J.; Broquist, H. P. J . Am. Chem. SOC.1968, 90, 5639 and references cited therein. (3) Guengerich, F. P.;Aust, S. D. Mol. Pharmacol. 1977, 13, 185 and references cited therein. (4) Clevenstine, E.C.; Broquist, H. P.; Harris, T. M. Biochemistry 1979, 18, 3659. Clevenstine, E. C.; Walter, P.; Harris, T. M.; Broquist, H. P. Ibid. 1979, 18, 3663. (5) (a) Cartwright, D.; Gardiner, R. A,; Rinehart, K. L. J. Am. Chem. Soc. 1970, 92, 7615. (b) Gensler, W.J.; Hu, M. W . J . Org. Chem. 1973, 38, 3848.
0002-7863/82/1504-7065$01.25/0
-a
0
control,sbbut it is not clear how selectively the stereochemistry contained in the six-membered ring of 1 was established. We now describe a completely new approach to slaframine that uses an intramolecular imino Diels-Alder cycloaddition6 as the key step to efficiently construct the indolizidine ring system and to set the stereochemistry of 1. Our starting material for the synthesis was readily available' diene aldehyde 2 which was treated with the carbanion derived from bis(trimethylsily1)acetamide (BSA)8 in THF at -78 OC, followed by an acidic workup, affording @-hydroxyamide 3 (68% (6) Khatri, N.A,; Schmitthenner, H. F.; Shringarpure, J.; Weinreb, S. M. J . Am. Chem. SOC.1981, 103, 6387 and references cited therein. (7) Erhart-Subramanian, K. E. C.; Huisman, H. 0.;de Koening, H. Synrh. Commun. 1973, 3, 25. (8) Morwick, T.Tetrahedron L e f t . 1980, 21, 3227. We have found that the use of sec-butyllithiumlTMEDA rather than n-butyllithium as originally reported significantly improved the yield of adduct 3.
0 1982 American Chemical Society
